Pre-operative Intra-nasal Dexmedetomidine or Insulin for Prevention of Early Post-operative Cognitive Dysfunction in Patients Undergoing Elective Coronary Artery Bypass Graft.

Pre-operative Intra-nasal Dexmedetomidine or Insulin for Prevention of Early Post-operative Cognitive Dysfunction in Patients Undergoing Elective Coronary Artery Bypass Graft. A Comparative Randomized Bi-centric Study

On pump coronary revascularization is a very common leading cause for post-operative cognitive dysfunction regarding patient age grouping and diffuse systemic inflammatory response induced by bypass machine . Many factors are incriminated as pre-operative sleep disturbance, previous history of neurocognitive dysfunction. The accumulating evidence refers to an incidence between 20-40% with majority among geriatric population. The primary pathology is still elusive and many trials are under evaluation. Neuro-inflammation, hypo perfusion, fat emboli and reperfusion injury are among the most postulative aetiologias. The corner stone in the pathology of postoperative cognitive dysfunction is abnormal sleep rhythm. Intra-nasal insulin can provide neuroprotection via providing insulin growth factor and obtund neuronal apoptosis , while dexmedetomidine can antagonize neural-degeneration via regulation of systematic inflammatory cytokines including interleukin 1β, tumor necrosis factor-α, and NF-κB, inhibiting the expressions of Toll-like receptor , and through α2 adrenoceptor-mediated anti-inflammatory pathways

Study Overview

• Status: Recruiting
• Conditions: Post Operative Cognitive Dysfunction
• Intervention / Treatment: Drug: intranasal saline group; Drug: intranasal insulin; Drug: Intranasal dexmedetomidine

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: mina raouf, MD; Phone Number: 01015752424; Email: drmina2015@gmail.com

Study Locations

• Egypt
  • Al Fayyum, Egypt
    • Recruiting
    • Fayoum University
    • Contact: Menofia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult population, 60 years or above, both sex, candidate for elective on pump coronary revascularization

Exclusion Criteria:

• patient refusal
• combined reperfusion and valve replacement operations.
• Emergency or redo CABG.
• preoperative MMSE score less than 20
• preoperative cardiomyopathy (ejection fraction <40%).
• previous history of cerebrovascular stroke or carotid endarterectomy, dementia, language, hearing or visual impairment precluding accurate neurocognitive assessment.
• history of heparin resistance.
• chronic use of hypnotics (>3 times weekly for >4 weeks), mood stabilizing drugs (lithium, Na valoprate, anticonvulsants) or melatonin.
• pre-operative pacing.
• recent nasal surgery (<3 months), prior maxillofacial trauma with nasal deformity, nasal polyposis or severe allergic rhinitis.
• severe obstructive sleep apnea (apnea hypopnea index >30), central sleep apnea or obesity-hypoventilation syndrome, and planned postoperative non-invasive ventilation.
• Chronic acholic population Alcohol Use Disorders Identification Test (AUDIT) score ≥8 for men or ≥7 for women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group	Drug: intranasal saline group; 3 ml of saline 0.9 % twice daily for 2 days preoperatively at fixed time ( 9 am and 6 pm)
Active Comparator: Dexmedetomidine group	Drug: Intranasal dexmedetomidine; 1.5 mic/kg on 3 ml saline 0.9% twice daily for 2 days preoperative via mucosal atomization device at fixed times ( 9 am, 6 pm)
Active Comparator: Insulin group	Drug: intranasal insulin; 20 IU of regular insulin on 3 ml saline 0.9% twice daily for 2 days preoperative via mucosal atomization device at fixed times ( 9 am, 6 pm)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini mental state examination	Acute cognitive assessment, score from 0-10 = severe sementia, 10-20 = moderate dementia, 20-25= mild , 25-30= questionably significabt	PREOPERATIVE, 1,3,5, 7 days , on hospital discharge (up to 3 weeks post operative) AND 3 months post operative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time for extubation	hours elapsed from ICU admission until extubation	6 hours
ICU stay	Days from ICU admission postoperative and discharge to word	one week
procedure related complication	bradycardia, spasm, cough,	3 days
serum glucose	serum glucose	1 day before surgery, at time of surgery, during bypass, 30 minutes after bypass at ICU admission, first day, second , third
Serum troponin	normal level < 0.12	preoperative, on admission, 1, 3 days, 5 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Richards-Campbell Sleep Questionnaire	sleep quality . The counting method was recorded with numbers (0 points to 100 points). The higher the score, the higher the sleep quality star.	DAILY ( EARLY MORNING at 8-9 AM ) THROUHGOUT ICU stay (10 DAYS)
Confusion assessment method - ICU	POST PERATIVE DELERIUM. CAM (yes or no) includes four aspects: (1) acute onset and fluctuat- ing course, (2) inattention, (3) incoherent thinking, and (4) altered consciousness; the presence of both (1) and (2), and one of (3) or (4) is diagnostic of POD With a total score of 30, a higher score indicates a lower incidence of neurocognitive dysfunction	TWICE DAILY UNTIL ICU DISCHARGE ( 10 DAYS)
transcranial doppler	Pulsatality index ( PI) > 0.8 means severe vasospasm	preoperative, 1 day, 3 days, 5, 7 days
transcranial doppler	resistive index .. 0.8> severe spasm	preoperative, 1 day, 3 days, 5, 7 days
change in MMSE	number and percentage of population with ≥2-point decline in MMSE from preoperative value	1,3,5,7 days from ICU admission and on hospital discharge (3 WEEKS POST OPERATIVE) AND AT 3 MONTHS POST OPERATIVE
Montreal cognitive assessment		preoperative and at 3 months post operative

Collaborators and Investigators

• Sponsor: Minia University

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2024
• Primary Completion (Estimated): May 14, 2026
• Study Completion (Estimated): May 15, 2026

Study Registration Dates

• First Submitted: December 14, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): December 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Postoperative Complications; Pathologic Processes; Neurocognitive Disorders; Cognition Disorders; Postoperative Cognitive Complications; Cognitive Dysfunction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Hypnotics and Sedatives; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Dexmedetomidine
• Other Study ID Numbers: 640/R

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No